combination of toripalimab and neoadjuvant chemoradiotherapy in esophageal cancer

Conditions: Esophageal Squamous Cell Carcinoma by AJCC V8 Stage; Resectable Esophageal Cancer

Summary: neoadjuvant chemoradiotherapy (crt) followed by surgery has become the standard treatment option for locally advanced esophageal cancer (ec). however, only 20% to 40% of ec patients can achieve pathologic complete response (pcr) after neoadjuvant crt with favorable prognosis. immunotherapy targeting the pd-1/pd-l1 checkpoints has demonstrated promising activity in advanced ec. the aim of this study was to evaluate the efficacy and safety of the combination of toripalimab (an anti-pd-1 antibody) combined with neoadjuvant crt in locally advanced esophageal squamous cell carcinoma (escc).


Eligibility criteria:
inclusion criteria: 1. a histopathological diagnosis of resectable thoracic esophageal squamous cell carcinoma with a pre-treatment clinical stage of t1-4an1-3m0 or t3-4an0m0 according to the 8th edition of the uicc staging system; 2. patients who are anti-tumor treatment-naive; 3. estimated life expectancy \>6 months 4. aged 18 to 70 years old of either gender 5. the function of important organs meets the following requirements: a. white blood cell count (wbc) ≥ 4.0×109/l, absolute neutrophil count (anc) ≥ 1.5×109/l; b. platelets ≥ 100×109/l; c. hemoglobin ≥ 9g/dl; d. serum albumin ≥ 2.8g/dl; e. total bilirubin ≤ 1.5×uln, alt, ast and/or akp ≤ 2.5×uln; f. serum creatinine ≤ 1.5×uln or creatinine clearance rate \>60 ml/min; 6. ps score of 0-1; 7. ability to understand the study and sign informed consent. exclusion criteria: 1. patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.); 2. known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin; 3. patients who have a preexisting or coexisting bleeding disorder; 4. other uncontrollable inoperable patients; 5. female patients who are pregnant or lactating; 6. inability to provide informed consent due to psychological, familial, social and other factors; 7. presence of ctc grade ≥ 3 peripheral neuropathy; 8. a history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer 9. a history of diabetes for more than 10 years and poorly controlled blood glucose levels; 10. patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia. 11. active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive hiv test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation; 12. a history of interstitial lung disease or non-infectious pneumonia; 13. a history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment; 14. presence of active hepatitis b (hbv dna ≥ 2000 iu/ml or 104 copies/ml), hepatitis c (positive for hepatitis c antibody, and hcv-rna levels higher than the lower limit of the assay).

Keywords: esophageal squamous cell carcinoma neoadjuvant chemoradiotherapy toripalimab pathologic complete response